A sustained-, delayed-, extended-, controlled- or anyway modified-release formulation can be prepared according to different known techniques:
Use of inert matrices, in which the main structural component is a highly lipophilic material having poor affinity to biological fluids, which affords some resistance to penetration of said fluids.
Use of hydrophilic matrices, in which the structural component affords a marked resistance to wetting and solubilization in biological fluids, as the system tends to form gels and to gradually swell in time.
Use of bioerodible and/or biodegradable matrices, in which the used polymers and materials gradually undergo metabolic and/or physiological degradation at certain biological sites.
Use of mixed matrices, which comprises the use of inert lipophilic matrices with hydrophilic systems or 3-matrix-systems, i.e. hydrophilic-amphiphilic-lipophilic matrices, where different interactions with different release kinetics take place.
All the above mentioned procedures suffer, however, from some drawbacks and disadvantages.
Inert matrices generally provide non-linear but exponential release kinetics of the active ingredient.
Hydrophilic matrices have at first a straight line dissolution profile then after a certain part of the active ingredient has been released, they deviate from release linearity.
Bioerodible and/or biodegradable matrices require the ideal enzyme and/or biological environment for the constant release of the drug.
Mixed matrices consist of suitably mixed lipophilic and hydrophilic matrices combined or by lipophilic, amphiphilic and hydrophilic matrices. Although being a progress as for modified release, they do not contain materials able to improve and guarantee restricted release of the drug as well as homogeneous absorption in the gastrointestinal tract, after the drug has been released.
When a modified-release formulation of a drug having either topical activity in the gastrointestinal tract or systemic activity is required, the controlled release has to be ensured from the very first moment after the administration. A somewhat homogeneous release range in time is also necessary, while ensuring, after an amount of the active ingredient has been released, the rapid activity of the drug both topically and systemically, thanks to it being present as microemulsion, solubilized or complexed.